Factors Associated with Carriage of Enteropathogenic and Non-Enteropathogenic Viruses: A Reanalysis of Matched Case-Control Data from the AFRIBIOTA Site in Antananarivo, Madagascar.

Environmental Enteric Dysfunction (EED) is an associate driver of stunting in poor settings, and intestinal infections indirectly contribute to the pathophysiology underlying EED. Our work aimed at assessing whether enteric viral carriage is determinant to stunting. A total of 464 healthy and asymptomatic children, aged 2 to 5 years, were recruited, and classified as non-stunted, moderately stunted, or severely stunted. Among the recruited children, 329 stool samples were obtained and screened for enteric and non-enteric viruses by real-time polymerase chain reaction. We statistically tested for the associations between enteric viral and potential risk factors. Approximately 51.7% of the stool samples were positive for at least one virus and 40.7% were positive for non-enteric adenoviruses. No statistical difference was observed between virus prevalence and the growth status of the children. We did not find any statistically significant association between viral infection and most of the socio-demographic risk factors studied, except for having an inadequate food quality score or an over-nourished mother. In addition, being positive for Ascaris lumbricoides was identified as a protective factor against viral infection. In conclusion, we did not find evidence of a direct link between stunting and enteropathogenic viral carriage in our population.

Cross-sectional cycle threshold values reflect epidemic dynamics of COVID-19 in Madagascar.

As the national reference laboratory for febrile illness in Madagascar, we processed samples from the first epidemic wave of COVID-19, between March and September 2020. We fit generalized additive models to cycle threshold (Ct) value data from our RT-qPCR platform, demonstrating a peak in high viral load, low-Ct value infections temporally coincident with peak epidemic growth rates estimated in real time from publicly-reported incidence data and retrospectively from our own laboratory testing data across three administrative regions. We additionally demonstrate a statistically significant effect of duration of time since infection onset on Ct value, suggesting that Ct value can be used as a biomarker of the stage at which an individual is sampled in the course of an infection trajectory. As an extension, the population-level Ct distribution at a given timepoint can be used to estimate population-level epidemiological dynamics. We illustrate this concept by adopting a recently-developed, nested modeling approach, embedding a within-host viral kinetics model within a population-level Susceptible-Exposed-Infectious-Recovered (SEIR) framework, to mechanistically estimate epidemic growth rates from cross-sectional Ct distributions across three regions in Madagascar. We find that Ct-derived epidemic growth estimates slightly precede those derived from incidence data across the first epidemic wave, suggesting delays in surveillance and case reporting. Our findings indicate that public reporting of Ct values could offer an important resource for epidemiological inference in low surveillance settings, enabling forecasts of impending incidence peaks in regions with limited case reporting.

Epidemiological Patterns of Seasonal Respiratory Viruses during the COVID-19 Pandemic in Madagascar, March 2020-May 2022.

Three epidemic waves of coronavirus disease-19 (COVID-19) occurred in Madagascar from March 2020 to May 2022, with a positivity rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) of 21% to 33%. Our study aimed to identify the impact of COVID-19 on the epidemiology of seasonal respiratory viruses (RVs) in Madagascar. We used two different specimen sources (SpS). First, 2987 nasopharyngeal (NP) specimens were randomly selected from symptomatic patients between March 2020 and May 2022 who tested negative for SARS-CoV-2 and were tested for 14 RVs by multiplex real-time PCR. Second, 6297 NP specimens were collected between March 2020 and May 2022 from patients visiting our sentinel sites of the influenza sentinel network. The samples were tested for influenza, respiratory syncytial virus (RSV), and SARS-CoV-2. From SpS-1, 19% (569/2987) of samples tested positive for at least one RV. Rhinovirus (6.3%, 187/2987) was the most frequently detected virus during the first two waves, whereas influenza predominated during the third. From SpS-2, influenza, SARS-CoV-2, and RSV accounted for 5.4%, 24.5%, and 39.4% of the detected viruses, respectively. During the study period, we observed three different RV circulation profiles. Certain viruses circulated sporadically, with increased activity in between waves of SARS-CoV-2. Other viruses continued to circulate regardless of the COVID-19 situation. Certain viruses were severely disrupted by the spread of SARS-CoV-2. Our findings underline the importance and necessity of maintaining an integrated disease surveillance system for the surveillance and monitoring of RVs of public health interest.

The COVID-19 epidemic in Madagascar: clinical description and laboratory results of the first wave, march-september 2020.

BACKGROUND: Following the first detection of SARS-CoV-2 in passengers arriving from Europe on 19 March 2020, Madagascar took several mitigation measures to limit the spread of the virus in the country. METHODS: Nasopharyngeal and/or oropharyngeal swabs were collected from travellers to Madagascar, suspected SARS-CoV-2 cases and contact of confirmed cases. Swabs were tested at the national reference laboratory using real-time RT-PCR. Data collected from patients were entered in an electronic database for subsequent statistical analysis. All distribution of laboratory-confirmed cases were mapped, and six genomes of viruses were fully sequenced. RESULTS: Overall, 26,415 individuals were tested for SARS-CoV-2 between 18 March and 18 September 2020, of whom 21.0% (5,553/26,145) returned positive. Among laboratory-confirmed SARS-CoV-2-positive patients, the median age was 39 years (IQR: 28-52), and 56.6% (3,311/5,553) were asymptomatic at the time of sampling. The probability of testing positive increased with age with the highest adjusted odds ratio of 2.2 [95% CI: 1.9-2.5] for individuals aged 49 years and more. Viral strains sequenced belong to clades 19A, 20A and 20B indicative of several independent introduction of viruses. CONCLUSIONS: Our study describes the first wave of the COVID-19 in Madagascar. Despite early strategies in place Madagascar could not avoid the introduction and spread of the virus. More studies are needed to estimate the true burden of disease and make public health recommendations for a better preparation to another wave.

Genetic diversity and molecular epidemiology of respiratory syncytial virus circulated in Antananarivo, Madagascar, from 2011 to 2017: Predominance of ON1 and BA9 genotypes.

BACKGROUND: Respiratory syncytial virus is the main cause of acute respiratory infections leading to a considerable morbidity and mortality among under-5 years children. A comprehensive scheme of RSV virus evolution is of great value in implementing effective universal RSV vaccine. OBJECTIVE: We investigated the clinical spectrum and molecular characteristics of detected RSV over a period of seven years (January 2011 to June 2017) in Antananarivo, the capital city of Madagascar. STUDY DESIGN: 671 nasopharyngeal samples taken from children aged less than 5 years suffered from ARI were screened for RSV by real-time PCR. Clinical data were retrieved from case report forms. Genotype identification was performed by reverse-transcription PCR and sequencing of the second hyper variable region (HVR2) of the G glycoprotein. RESULTS: Amongst samples tested, 292 (43.5 %) were found positive for RSV. RSV A predominated during the study period which accounted for 62.3 % (182/292) of positive samples while RSV B represented 37.0 % (108/292). Phylogenetic analyses identified NA1 and ON1 genotypes among RSV A. Though NA1 widespread from 2011 to 2013, ON1 became prevalent during the following years. Among RSV B, THB, CB1 and BA9 genotypes were detected. A co-circulation of THB and CB1 strains occurred during the 2011 season that was substituted by the BA9 from 2012. Malagasy ON1 strains carried some characteristic amino acid substitutions that distinguish them from the worldwide ON1 strains. By analyzing clinical spectrum, ON1 and BA genotypes seemed to prevail in mild infections compared to NA1. CONCLUSION: Results obtained here will have its implication in predicting temporal evolution of RSV at the local level. Considering the insularity of the country, information obtained should help in comparative analysis with global RSV strains to optimize vaccine efficacy.

The ribotoxin deoxynivalenol affects the viability and functions of glial cells.

Glial cells are responsible for maintaining brain homeostasis. Modification of the viability and functions of glial cells, including astrocytes and microglia, are associated with neuronal death and neurological diseases. Many toxins (heavy metals, pesticides, bacterial or viral toxins) are known to impact on brain cell viability and functions. Although recent publications suggest a potential link between environmental exposure of humans to mycotoxins and neurological diseases, data regarding the effects of fungal toxins on brain cells are scarce. In the present study, we looked at the impact of deoxynivalenol (DON), a fungal ribotoxin, on glial cells from animal and human origin. We found that DON decreased the viability of glial cells with a higher toxicity against microglial cells compared with astrocytes. In addition to cellular toxicity, DON affected key functions of glial cells. Thus, DON caused a biphasic effect on the neuroinflammatory response of microglia to lipopolysaccharide (LPS), while sublethal doses of DON increased the LPS-induced secretion of TNF-α and nitric oxide, toxic doses inhibited it. In addition to affecting microglial functions, sublethal doses of DON also suppressed the uptake of L-glutamate by astrocytes. This inhibition was associated with a modification of the expression of the glutamate transporters at the plasma membrane. Our results suggest that environmental ribotoxins such as DON could, at low doses, cause modifications of brain homeostasis and possibly participate in the etiology of neurological diseases in which alterations of the glia are involved.

The food-associated fungal neurotoxin ochratoxin A inhibits the absorption of glutamate by astrocytes through a decrease in cell surface expression of the excitatory amino-acid transporters GLAST and GLT-1.

The food-associated mycotoxin ochratoxin A (OTA) has been demonstrated to be deleterious to numerous cell types including brain cells. Although OTA has been proved to be toxic to astrocytes, no other investigation has been conducted on the impact of OTA on astrocytic functions. In the present study, we evaluated the effect of OTA on one of the major astrocytic functions, i.e. the reabsorption of extracellular glutamate. We found that OTA suppressed glutamate absorption by rat cortical astrocytes with a half inhibitory concentration of 1.3 and 10.1 microM in the absence and presence of fetal calf serum. Although OTA inhibits glutamine synthetase activity, this effect was not involved in OTA-mediated alteration of glutamate absorption since decrease in enzyme activity only occurred at high cytotoxic concentrations of toxin (100 microM). Similarly, alterations in the expression of the excitatory amino-acid transporters were not involved since OTA failed to modify total expression level of GLAST and GLT-1. We found that inhibition of glutamate absorption by OTA was due to a decrease in the expression of GLAST and GLT-1 at the cell surface. We propose that, in addition to being directly toxic to neurons and astrocytes, OTA could also cause the death of brain cells through inhibition of glutamate uptake by astrocytes, leading to the accumulation of extracellular glutamate and ultimately to excitotoxicity.